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Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways.
Int J Biochem Cell Biol. 2008; 40(11):2572-82.IJ

Abstract

Caffeic acid phenethyl ester has been shown to have anti-inflammatory and anti-cancer effects. We examined the effects of caffeic acid phenethyl ester on lipopolysaccharide-induced production of nitric oxide and prostaglandin E2, and expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages. We also investigated the effects of caffeic acid phenethyl ester on lipopolysaccharide-induced septic shock in mice. Our results indicate that caffeic acid phenethyl ester inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in a concentration-dependent manner and inhibits inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 cells, without significant cytotoxicity. To further examine the mechanism responsible for the inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by caffeic acid phenethyl ester, we examined the effect of caffeic acid phenethyl ester on lipopolysaccharide-induced nuclear factor-kappaB activation and the phosphorylation of mitogen-activated protein kinases. Caffeic acid phenethyl ester treatment significantly reduced nuclear factor-kappaB translocation and DNA-binding in lipopolysaccharide-stimulated RAW 264.7 cells. This effect was mediated through the inhibition of the degradation of inhibitor kappaB and by inhibition of both p38 mitogen-activated protein kinase and extracellular signal-regulated kinase phosphorylation, at least in part by inhibiting the generation of reactive oxygen species. Furthermore, caffeic acid phenethyl ester rescued C57BL/6 mice from lethal lipopolysaccharide-induced septic shock, while decreasing serum levels of tumor necrosis factor-alpha and interleukin-1beta. Collectively, these results suggest that caffeic acid phenethyl ester suppresses the induction of cytokines by lipopolysaccharide, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression, by blocking nuclear factor-kappaB and p38/ERK activation. These findings provide mechanistic insights into the anti-inflammatory and chemopreventive actions of caffeic acid phenethyl ester in macrophages.

Authors+Show Affiliations

Department of Marine Life Science, Chosun University, Gwangju 501-759, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18571461

Citation

Jung, Won-Kyo, et al. "Caffeic Acid Phenethyl Ester Protects Mice From Lethal Endotoxin Shock and Inhibits Lipopolysaccharide-induced Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression in RAW 264.7 Macrophages Via the p38/ERK and NF-kappaB Pathways." The International Journal of Biochemistry & Cell Biology, vol. 40, no. 11, 2008, pp. 2572-82.
Jung WK, Choi I, Lee DY, et al. Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways. Int J Biochem Cell Biol. 2008;40(11):2572-82.
Jung, W. K., Choi, I., Lee, D. Y., Yea, S. S., Choi, Y. H., Kim, M. M., Park, S. G., Seo, S. K., Lee, S. W., Lee, C. M., Park, Y. M., & Choi, I. W. (2008). Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways. The International Journal of Biochemistry & Cell Biology, 40(11), 2572-82. https://doi.org/10.1016/j.biocel.2008.05.005
Jung WK, et al. Caffeic Acid Phenethyl Ester Protects Mice From Lethal Endotoxin Shock and Inhibits Lipopolysaccharide-induced Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression in RAW 264.7 Macrophages Via the p38/ERK and NF-kappaB Pathways. Int J Biochem Cell Biol. 2008;40(11):2572-82. PubMed PMID: 18571461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways. AU - Jung,Won-Kyo, AU - Choi,Inhak, AU - Lee,Da-Young, AU - Yea,Sung Su, AU - Choi,Yung Hyun, AU - Kim,Moon-Moo, AU - Park,Sae-Gwang, AU - Seo,Su-Kil, AU - Lee,Soo-Woong, AU - Lee,Chang-Min, AU - Park,Yeong-Min, AU - Choi,Il-Whan, Y1 - 2008/05/15/ PY - 2008/01/14/received PY - 2008/04/04/revised PY - 2008/05/05/accepted PY - 2008/6/24/pubmed PY - 2008/10/9/medline PY - 2008/6/24/entrez SP - 2572 EP - 82 JF - The international journal of biochemistry & cell biology JO - Int J Biochem Cell Biol VL - 40 IS - 11 N2 - Caffeic acid phenethyl ester has been shown to have anti-inflammatory and anti-cancer effects. We examined the effects of caffeic acid phenethyl ester on lipopolysaccharide-induced production of nitric oxide and prostaglandin E2, and expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages. We also investigated the effects of caffeic acid phenethyl ester on lipopolysaccharide-induced septic shock in mice. Our results indicate that caffeic acid phenethyl ester inhibits lipopolysaccharide-induced nitric oxide and prostaglandin E2 production in a concentration-dependent manner and inhibits inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 cells, without significant cytotoxicity. To further examine the mechanism responsible for the inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by caffeic acid phenethyl ester, we examined the effect of caffeic acid phenethyl ester on lipopolysaccharide-induced nuclear factor-kappaB activation and the phosphorylation of mitogen-activated protein kinases. Caffeic acid phenethyl ester treatment significantly reduced nuclear factor-kappaB translocation and DNA-binding in lipopolysaccharide-stimulated RAW 264.7 cells. This effect was mediated through the inhibition of the degradation of inhibitor kappaB and by inhibition of both p38 mitogen-activated protein kinase and extracellular signal-regulated kinase phosphorylation, at least in part by inhibiting the generation of reactive oxygen species. Furthermore, caffeic acid phenethyl ester rescued C57BL/6 mice from lethal lipopolysaccharide-induced septic shock, while decreasing serum levels of tumor necrosis factor-alpha and interleukin-1beta. Collectively, these results suggest that caffeic acid phenethyl ester suppresses the induction of cytokines by lipopolysaccharide, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression, by blocking nuclear factor-kappaB and p38/ERK activation. These findings provide mechanistic insights into the anti-inflammatory and chemopreventive actions of caffeic acid phenethyl ester in macrophages. SN - 1357-2725 UR - https://www.unboundmedicine.com/medline/citation/18571461/Caffeic_acid_phenethyl_ester_protects_mice_from_lethal_endotoxin_shock_and_inhibits_lipopolysaccharide_induced_cyclooxygenase_2_and_inducible_nitric_oxide_synthase_expression_in_RAW_264_7_macrophages_via_the_p38/ERK_and_NF_kappaB_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1357-2725(08)00197-0 DB - PRIME DP - Unbound Medicine ER -